Optimization of dextran sulfate/poly-l-lysine based nanogels polyelectrolyte complex for intranasal ovalbumin delivery

The emerging trend in new vaccine development is to identify protective antigens and develop peptide-based vaccines able to offer a better immunogenicity/risk ratio. Nanogel (nGEL) can be designed to optimally present the delivered antigen to the immune system in controlled release formulations promoting their targeting to specific immune populations. Final properties of nGEL (size, surface charge) may be determining factors in designing the induced immune response. Taking into account these considerations, the aim of the study is the design of nGEL based on Dextran Sulfate (DS) and ϵ-Poly-lysine (εPL) of tunable size and surface charge by Response Surface Methodology (RSM) approach for nasal administration. nGEL systems were obtained by a mild and environmental-friendly physical cross-linking method. Based on the desirability function, the optimized formulation showed similar observed and predicted responses (errors <10%) in terms of mean size, polidispersity and surface charge. Stability studies were performed by Turbiscan® AGS technology on nGEL stored at 25 ◦C and 37 ◦C for 2 weeks and by dynamic light scattering on nGEL stored at 4 ◦C, 25 ◦C and 37 ◦C for 6 months. Citotoxicity evaluation was performed on HFF1, NCTC and Calu-3 cells after 24 h of treatment by MTT assay proving the safety of the optimized nGEL (≤0.117 mg/mL). The optimized formulation was successfully loaded with ovalbumin (OVA) as a model antigen and furtherly characterized for thermal behavior, encapsulation efficiency and in vitro release profile in phosphate buffer solution pH 5.8 to simulate the intranasal milieu. Loaded nGEL released nearly 43% of OVA within 72 h, assuring prolonged release to maximize exposure to the immune system.